Targeted and template cores were taken by a single urologist at UCLA Clark Urology Center under local anesthesia using a MR/US fusion and biopsy tracking device .A dedicated uro-pathologist interpreted all biopsy cores . FT eligibility was assessed using three different ablative strategies to determine the extent of ablation that would be needed to eliminate the index lesion. Individual biopsy cores from each subject were assessed using database software to determine eligibility for each strategy. Men with positive biopsy cores limited to the ROI were considered eligible for all FT strategies . Men with positive cores adjacent to the ROI were considered eligible for quadrant and hemi-ablation. Those with ipsilateral but distant positive cores were considered eligible for hemi-ablation. A visual representation of different strategies can be seen in Figure 3. We evaluated eligibility using both a GS ≤ 4+3 and GS ≤ 3+4 threshold .Of the 454 men with biopsy positive ROI, 64 underwent radical prostatectomy and whole mount processing to facilitate MRI-histological correlation as previously described.7 Three-dimensional printed molds were used in cases processed after 2014. Lesion contours identified on whole mount histology were loaded onto custom software and elastically warped to match the mpMRI-defined prostate contour, allowing targets on mpMRI to be directly compared to lesions identified on whole mount histology. Eligibility for FT was then re-assessed based on evaluation of whole mount sections by a dedicated urologic pathologist . Descriptive statistics for patient characteristics were calculated for each group. Confidence intervals were calculated using a binomial assumption at a 95% threshold. KruskalWallis non-parameteric one-way analysis of variance and post-hoc tests were conducted to measure differences between continuous variables.
Pearson chi-squared tests were performed on categorical variables. Statistical significance was considered at p < 0.05 for all analyses. Statistical analyses were performed by a coauthor using Stata® software, version 13.1. Additional analyses were performed using JMP Pro,vertical agriculture version 13. 1408 men in our cohort underwent MRI/US fusion biopsy from 2010–2016. 454 men met the screening criteria in Figure 1. Of the 454 men with at least one biopsypositive ROI, 175 FT candidates were identified. Of the 914 men with a MRI suspicion score or higher, 19% were FT candidates . 57 men with small-volume GS 3+3 cancers were found . Eight men who would have otherwise qualified for FT were excluded on the basis of PSA > 20 ng/mL. Baseline patient characteristics for FT eligible and ineligible patients are shown in a supplementary table . Men were considered ineligible if the ROI contained either insignificant CaP or high-risk CaP. Eligible and ineligible men differed in age, ethnicity, free PSA and PSA density, mpMRI suspicion score, average number of positive cores, incidence of bilateral CaP, MCCL, and GS . While differences between components of inclusion criteria are expected, post-hoc tests nonetheless showed an increasing trend across all three categories with total PSA, PSA density, number of positive cores, and maximum cancer core length. Of the patients with GS ≤ 3+4, 154 were eligible for hemi-ablation or less, 140 for quadrant ablation or less, and 94 for site-specific ablation. When the inclusion criteria included those with maximum GS 4+3, 175 were eligible for hemi-ablation or less, 157 for quadrant ablation or less and 105 for site specific ablation . No man within this study is known to have undergone focal Therapy.64 men in this series underwent RP as first-line therapy with whole-mount processing of the specimen; 35/64 with 3D-printed molds. Average time from biopsy to surgery was 89.1 ± 32.5 days.
Examples of whole mount histology and 3D digital reconstruction are demonstrated in Figure 3. 25/64 patients who underwent RP would have qualified for FT on the basis of biopsy findings. 15/64 men qualified for FT on the basis of whole mount histological findings, with 16 discordant findings . Of the 13 patients who were classified as eligible for FT based on fusion biopsy and did not qualify based on whole mount , 4 were discordant due to a higher GS on whole mount, and 9 were due to the lesion crossing the midline. When examining factors associated with eligibility determined after RP, no significant difference was found for PSA density , prostate volume , or total serum PSA , although the study was not powered for analysis on whole-mount prostatectomy cases. Targeted and template biopsy, when combined, had a sensitivity, specificity, and accuracy of 80.0%, 73.5%, and 75.0%, respectively for determining eligibility for FT when compared to the whole mount gold standard. Targeted cores alone yielded a sensitivity of 73.3% , and a specificity of 47.9% , with an accuracy of 54.7% . FT has recently emerged as a potentially definitive treatment for localized CaP that aims to preserve quality of life.FT appears promising in initial studies using HIFU, cryotherapy, and FLA,but long-term oncological control has not been established. One key barrier is knowing a priori which patients will benefit from partial treatment,with some arguing for FT as an alternative to surgical intervention, and others for FT as a complement to active surveillance.While the multi-focality of CaP favors whole gland treatment, studies have emphasized the importance of the index lesion as a driver of metastatic potential.Recent studies indicate that low grade, low volume lesions behave in an indolent fashion, with limited metastatic potential.Contrasting these is a case report by Haffner and colleagues which investigated the clonal origin of lethal prostate cancer and found that its origin arose from a small, low-grade cancer focus in the primary tumor.
Nevertheless, more recent and larger studies continue to support the concept that CaP is driven by a single clone,and can be serially tracked with biomarkers and targeted biopsy.Furthermore, FT has been used successfully in treatment of other multifocal solid organ malignancies where secondary lesions have proven to be indolent.In the present study we estimated the proportion of men diagnosed by MRI/US fusion biopsy who would be eligible for FT. Eligibility criteria from a recent FDA-AUA-SUO workshop on partial gland ablation were used.6 Biopsy findings were also compared to whole mount histology in a subset of cases. We found that over a third of men with a MRI target and fusion biopsy-confirmed cancer were suitable candidates for FT; nearly a quarter met criteria for site-specific ablation. Fusion biopsy findings were generally concordant with whole mount findings, in agreement with findings shown previously.The majority of the false positives was attributed to the lesion crossing the midline. In this study, we called lesions that crossed the midline by even a few millimeters as ineligible for any method of focal therapy. In practice, many of these lesions are treatable using a site-specific ablation or ‘hockeystick’ ablation as described by Ahmed et al. Only in a minority of cases was assessment through targeted biopsy a failure due to upgrading. While eligibility criteria included GS ≤ 4+3 lesions, 89% of patients met more stringent criteria limited to GS ≤ 3+4. The increased sensitivity of MRI-targeted biopsy for detection of csCaP, widely reported for other situations, also appears valuable when evaluating for FT eligibility. In our work, over half of eligible men had csCaP localized to within a single ROI, while 40% of men had csCaP outside the index lesion. Both targeted and template biopsies were important in accurately classifying patients for FT. Overall accuracy using both methods was improved by 20% over using targeted biopsy alone . This suggests that the combined targeted and template biopsy approach is effective at ruling out focal therapy. While whole mount histology of RP specimens are generally concordant with targeted biopsy findings,the moderate agreement in eligibility assessment indicates that improved criteria need to be established. In the univariate analysis of eligible and ineligible patients, PSA density was significantly different between all three cohorts. While the RP data did not show a similar significant difference in PSA density,vertical farming aeroponics the difference suggests that PSA density merits further investigation as a eligibility criterion in a larger, powered study.While one potential source of error is the registration accuracy between MRI and US ,a larger issue is the underestimation of true tumor burden by MRI. of eligible patients had csCaP ipsilateral and adjacent to the ROI, qualifying for quadrant ablation. Le Nobin et al found that tumors required a 1 cm margin to achieve complete treatment, while Priester et al found that the average uniform margin to achieve complete treatment exceeded 1.5 cm.This supports the notion that biopsy cores should be taken from beyond the margins of the ROI when evaluating for site-specific or quadrant-based FT.
Moreover, these data suggest customization of focal therapy based on data from individual biopsy site locations around the apparent tumor margin.This also suggests that perhaps improved criteria for FT would include individual consideration of the position and size of the lesion, i.e. patient-specific planning, rather than uniform classification. Several limitations exist that preclude a more general interpretation of the findings presented. This study was hypothesis-generating and retrospective in nature, and was conducted at a single site with all biopsies performed by a single physician. Limited data were available for comparing fusion biopsy findings with whole mount histology. Nevertheless, the significant concordance between the two approaches for determining FT candidacy suggests that fusion biopsy may serve as an important aid to determine eligibility. Further, these results might be used to develop a framework for future prospective studies. The present findings suggest that more than one-third of patients with a biopsy-proven target were eligible for FT using consensus criteria; fusion biopsy with both targeting and template samples accurately characterizes the grade and extent of CaP for the purposes of determining FT eligibility Barrett’s esophagus is a risk factor for the development of esophageal adenocarcinoma .Challenges in the management of patients with BE include detecting areas of dysplasia or superficial cancer and surveillance after endoscopic treatment to evaluate for residual or recurrent disease. Dysplasia in BE may not be apparent during inspection using white light endoscopy . Therefore, current guidelines recommend endoscopic surveillance of BE with random 4-quadrant biopsy sampling every 1– 2 cm , in addition to targeted biopsy sampling of any visible abnormalities.This imperfect surveillance protocol can result in missed disease, with an estimated 25.3% of EAC procedures occurring within 1 year of a surveillance endoscopy.Dysplasia can be treated with endoscopic therapies including endoscopic mucosal resection ,radio frequency ablation ,cryotherapy,and others. However, high recurrence rates have been reported, including up to 33% recurrence of intestinal metaplasia or dysplasia at 2 years in the case of RFA.Residual disease, particularly at the GEJ, and the existence of disease buried beneath neosquamous epithelium are also sources of concern.Recently, advanced imaging techniques such as narrow band imaging and confocal laser endomicroscopy have sought to improve dysplasia detection in BE patients by allowing biopsies to be taken in a targeted rather than random fashion, even when focal abnormalities are absent on WLE inspection.Volumetric laser endomicroscopy utilizes optical coherence tomography to produce high-resolution, cross sectional surface, and subsurface images of the esophageal wall over a long continuous segment .Studies have examined the efficacy of VLE as applied to dysplasia detection in pre and post treatment surveillance as well as informing treatment selection.While the safety and feasibility of esophageal VLE imaging has been shown,the objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to BE management.This is a prospective observational cohort study from August 2014 to April 2016. Patients were eligible for inclusion in this study if undergoing a clinically indicated upper endoscopy during which VLE was used for evaluation of the esophagus. Procedures were performed at 18 centers throughout the United States . Each site was eligible to enroll up to 100 subjects, with an overall registry enrollment cap of 1000 patients. Investigators were free to recruit patients with a variety of disease states at various stages of clinical management. Patients for whom the VLE device would be in conflict with the manufacturer’s Instructions For Use were excluded. This included use in anatomies where catheter deployment would generate significant risk, such as the setting of a tight stricture. The research protocol and informed consent forms were approved by each of the participating institutional review boards, and informed consent was obtained from each participant prior to enrollment.